Process of producing 1-phenyl-2, 3-dimethyl-5-pyrazolone



Patented June 18, 1935 IRQCESS (BF PRODUCING 1PHENYL-2,3-

. DlME'EHYL-5-PYBAZOLONE Baptist Renter, Krailling-Planegg, Germany No Drawing. Application November 28, 1932,

Serial No. 1928 13 Claims.

l-phenyl-B-methyl pyrazolone is usually methylated on a technical scale by dissolving it in methyl alcohol and heating it togetherwith alkyl halides under high pressure. When ethyl bromide is used in this process several drawbacks are involved. This substance has a very low boiling point and is poisonous so that the use of same in some cases has caused the death of persons handling it. Moreover, the methylation with alkyl halides must be performed in enamelled vessels which relatively frequently must be renewed. During the series of operations, the autoclaves must also from time to time be tightened again in order to avoid losses of alkyl halides and the escape of dangerous gases. In the autoclaves the explosive methyl ether is formed and the methylation is driven beyond the dimethyl compound.

In the Bulletin de la Socit Chimique, vol. (4) 39, page 321, Rodionow has given some short informations about the effect exerted by p-toluene-sulfonic-acid methyl ester on technical pyrazolone when no solvent is present. He describes merely the formation of a compound whichhas a solidification point of 91-92" C. and which he regards as the methyl-p-toluenesulfonate oi the pyrazolone.

I have now found that in the melt an intermediate product is formed, which is not obtained in the form of l-phenyl-2,3-dimethyl5-pyrazo-- lone when working in the usual manner. When working after the usual method, which comprises the steps of adding alkali to the melt and shaking the oil together with the benzene, this'intermediate product is obtained in the form of a dark oil, which is insoluble in benzene and is'not obtained in the form of a p-toluene-sulfonicacid salt at the separation. The intermediate or by-products include compounds which possess the following formulae:

SOs-CelL-CHa In Germany Aprilv 12,

I onto-c N These compounds formed in addition to the 1- phenyl-2,3-dimethyl-5-pyrazolone in the melt are described in the following description and claims as quaternary bases, lay-products, or intermediate products. By treating these compounds separately or still better by treating the total methylated melt for about 2 hours at 100 C. with alkalies in excess said compounds will be completely converted. into l-phenyl-2,3-dimethyl-5-pyrazolone. When methylating without this alkali treatment only yields of about 83% of 1-phenyl-2,3-dimethyl-E-pyrazolone are obtained. Through the said treatment, however, the yield of 1-pheny1-2,3-dimethyl-5-pyrazolone is increased to 93% and the yield of p-toluene-sulfonic-acid salt is increased even to 95%. According to the information given by Rodionow the yield of toluene-sulfonic-acid salt amounts only to 50%. I have also found, that the toluene-sulfonic-acid salt will separate out almost quantitatively when the solution is made distinctly acid by means of mineral acids.

EXAMPLES WITH P-TOLUENE-SULFONIC-ACID METHYL ESTER I. MErnYLArIoN 174 g. of 1-phenyl-3-methyl-5pyrazolone and 195 g. of p-toluene-sulfonic-acid methyl ester are heated under stirring. At 130 C. a hardly perceptible foaming takes place. The temperature is thereupon raised to 150 C. and maintained at 150-160" C. for about 5-6 hours. The end product is a transparent melt, which is dissolved by adding 150 ccm of water and 8'7 g. of a solutionof caustic soda (46%). Thereupon additional 44 g. of caustic soda is added, whereby a deposit is formed and the mass is now boiled under stirring for about 2 hours on a reflux cooler. Instead of the caustic soda corresponding amounts of alkali metal carbonates may be used. The charge is cooled and 190 g. of hydrochloric acid (30%) are added under stirring and cooling, whereupon after some time the toluene-sulfonic-acid salt separates out in theiorm of a precipitate. This substance will also separate out at once when the fluid is activated by means of some crystals of the toluene-sulfonicacid salt. In hot water super-saturated solutions of the salt are formed and it is therefore necessary to add traces of the crystallized compound in order to initiate the crystallization. The product is sucked off through a lfilter and rinsed with water which has been slightly acidulated with hydrochloric acid. The salt is dried in vacuum or at 30-35 C. At still higher temperatures the salt will melt to a vitreous mass. This mass dissolves in boiling water and is diflicultly soluble in ligroin, benzene, alcohol and ether as well as in cold water and particularly in water containing some acid. In bicarbcnates and other alkaline solvents the salt dissolves very easily. When super-saturating with strong caustic alkalies 1-phenyl-2,3-dimethyl-5-pyrazolone and sodium p-toluene-sulfonate will separate out.

The product is apparently a compound comprising 1 molecule of p-toluene-sulfonic-acid, 1 molecule of l phenyl-2,3-dimethyl-5-pyrazolone and 2 molecules of crystal water. Yield: of the theoretically calculated amount. The precipitation of the salt may also be performed in two stages by dissolving the methylated melt in 150 com. of hot water and allowing the product to crystallize under cooling and stirring after having added hydrochloric acid until reaction is obtained with Congo red. The crystals are, as described above, washed and dried. This is crystallization I. The intermediate products formed at the methylation are in this case present in the filtrate of the crystallization and this must, therefore, also be treated with caustic al- Kali. The product is evaporated until a highly,

concentrated fluid is obtained and this fluid is made strongly alkaline and boiled for about 2 hours on a reflux cooler. Thereupon hydrochloric acid is added until an acid reaction is obtained with Congo red, whereupon the product is stirred in cold state for about half an hour, sucked through a filter, rinsed and dried in the manner described above.

This is crystallization II. Before product is subjected to further treatment, it is mixed with crystallization I.

2. Direct separation of the base from the toluene-suZfonic-acid-ester melt The methylation melt obtained after Example 1 is dissolved in 150 com. of water and boiled understirring for about 2'hours together with 150 g. of a caustic soda solution or a corresponding amount of other strong alkalies. The mass is thereupon cooled to about 7-0 C. and twice extracted with 500 ccm of benzene whilst still hot. The l-phenyl-2,3-dimethyl-5-pyraaolone passes into solution whereas the sodium toluenesulfonate remains undissolved. The fluid is 'separated from the sodium toluene sulfonateby suction or centrifugation and washed with benzene. The caustic soda and the benzene solution in the filtrate are also separated. When distilling off the benzene l-phenyl-2,3-dimethyl-5-pyrazolone in extremely pure state is left.

3. Producing of the 'base from the p-toluenesulfonate 378 g. of the salt obtained in accordance with Example 1 are heated together with com. of water and 120 g. of a caustic soda solution (35%) for abouthalf an hour in a water bath and extracted with benzene whilst still hot. After the removal of the benzene a very pure 1- pheny1-2,3-dimethyl-5-pyrazolone is left.

II. METHYLATION on THE l-PHENYL-3-METHYL-5-PY- RAZOLONE WITH DIMETHYL SULFATE 174 g. of 1-phenyl-3-methyl-5-pyrazolone and 120 g. of dimethyl sulphate (95% of the theoretically calculated amount) are mixed and heated very cautiously in order to prevent a sudden reaction. At 100 C. the temperature will automatically be raised to about C. When the increase of temperature ceases the mass is heated to about -160 C. and this temperature is maintained for about 6 hours. Thereupon 50 com. of water and subsequently g. of a caustic soda solution (35%) are added under stirring and the charge is heated to about 100 C. for 2 hours on a reflux cooler. Instead of a caustic soda solution also other alkalies,

such as carbonates or a mixture of alkali hydroxides and carbonates may be used. The base is separated out by means of benzene exactly in the same manner as described in connection with the toluene-sulfonic-acid process. If it is desired to separate out the intermediate product (instead of converting it directly into l-phenyl- 2,3dimethyl-5pyrazolone in the -manner .described above) the melt is dissolved in 50 com. of Water, whereupon 195 g. of NaOH are added and the product isextraoted with benzene without further heating. Between the benzene and the caustic soda solution a dark oil remains in undisso'lved state and this oil is the intermediate product.

This intermediate product is separated from the benzene and the caustic soda solution, dissolved in thrice the amount of water and heated to about 106 C. together with the excess of alkali for about 2 hours. After this treatment an oil is left which dissolves completely in benzene. When the benzene has distilled off, tests will show that this product is l-phenyl-2,3-dimethyl-S-py-razolone.

Yield:.90-92% of the amount.

I'claim:

1. A process for producing l-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting '1-phenyl-3-methyl 5 pyrazolone with an alkylating agent in the absence of a solvent. at an elevated temperature, thereby producing a melt, and treating said melt with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time.

2. A process for producing l-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting l-phenyl-B-methyl 5 pyrazolone with an alkylating agent in the absence of a solvent at an elevated temperature, thereby producing a melt, dissolving said melt, adding thereto a solution of a caustic alkali, extracting said resulting mixture with benzene, separating out the quaternary bases resulting, and treating said quaternary bases with an excess of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time.

3. A process for producing 1-phenyl-2,3-dimethyl-E-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl 5 pyrazolone with p-toluenesulphonic-acidmethyl-ester in the absence of a solvent at an elevated temperature,

theoretically calculated thereby producing a melt, dissolving said melt, 75

addingthereto a solution of acaustic alkali, extracting the resultant mixture with benzene, separating out the quaternary bases formed, and treating said quaternary bases with an excess amount of a compound of the groupconsisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time in order to convert said quaternary bases into the desired product. i

4. A process for producing l-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting l-phenyl-S-methyl 5 pyrazolone with dimethyl sulphate in the absence of a solvent at an elevated temperature, thereby producing a melt containing quaternary bases, and then treating said melt with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 'C; for a relatively long period of time'in order to convert the melt containing said quaternary bases into the desired product.

5. A process for producing 1pl1enyl-2,3-dimethyl-B-pyrazolone which comprises the steps of reacting l-phenyl-3- methyl 5 pyrazolone with dimethyl sulphate in the absence of a solvent at an elevated temperature, thereby producing a melt, dissolving said melt, adding thereto a solution of a caustic alkali, extracting with benzene, separating out the quaternary bases resulting, and then treating said bases with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at substantially100 C. for a relatively long period of time in order to convert said bases into the desired product.

6. A process for producing 1-phenyl-2,3-di methyl-5-pyrazolone which comprises the steps of reacting l-phenyll-methyl 5 pyrazolone with an alkylating agent in the absence of a solvent at an elevated temperature, thereby producing a melt containing quaternary bases, treating said melt with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time in order to convert said bases into the desired product, extracting said melt while still warm with benzene, and then removing the benzene to isolate the desired product.

7. A process for producing 1-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting l-phenyl-3-methyl-5-pyrazolone with an alkylating agent in the absence of a solvent at an elevated temperature, thus forming a mixture containing a salt of 1-phenyl-2,3-dimethyl- 5-pyrazolone together with quaternary bases, treating said mixture with an excess amount of a compound of the group consisting of an alkalimetal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time in order to convert said quaternary bases into the desired product, acidulating the resultant mixture with a mineral acid in order to separate the salt of 1-phenyl- 2,3-dimethyl-5-pyrazolone, isolating said salt by filtering, heating it with a solution of a caustic soda for a relatively long period of time, thus forming the desired product, extracting said product while the mixture is still warm with benzene, and then removing the benzene to iso late said product.

8. A process for producing l-phnyl-ZB-dimethyl-S-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with p-toluene sulphonic-acid-methyl-ester, thereby producing a mixture containing the salt of l-phenyl-2,B-dimethyI-S-pyrazolone with p-toluenesulphonic acid together with quaternary bases, adding to said mixture a solution of caustic soda, extracting the resultant mixture with benzene, removing the quaternary bases present in said mixture, treating said quaternary bases withan excess amount of a compound of the group con- 'sisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long'period of time in order to convert said quaternary bases into the desired product, aoidulating the mixture from which said quaternary bases have been extracted with a mineral acid in order to separate the p-toluene-sulphonic acid salt of 1phenyl2,3 dimethyl-5-pyrazolone, isolating said salt by filtering, heating said salt with a solution of caustic soda for a relatively longperiod of time, extracting said resultant mixture while it is still warm with benzene, and then removing the benzene to isolate the desired product.

9. A process for producing 1-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with p-toluene-sulphonic-acid-methyl-ester in the absence of a solvent at an elevated temperature, thereby producing a melt containing quaternary bases, treating said melt with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time in order to convert said quaternary bases into the desired product, extracting the mixture while it is still warm with benzene, and then removing the benzene in order to isolate the product.

10. A process for producing 1-phenyl-2,3-dimethyl-S-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with p-toluene-sulphonic-acid-methyl-ester in the absence of a solvent at an elevated temperature, thereby producing a melt, dissolving said melt, adding a solution of caustic alkali thereto, extracting said mixture with benzene, separating out the quaternary bases formed by the reaction which are still present in the mixture, treating said quaternary bases with an excess amount of a compound of the group consisting of an alkalimetal hydroxide and an alkali-metal carbonate at substantially 100 C. for a relatively long period of time in order to convert said bases into the desired product, extracting said resulting mixture while it is still warm with benzene, and then removing the benzene in order to isolate the desired product.

11. A process for producing 1-phenyl-2,3-dimethyl-5-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with dimethyl sulphate in the absence of a solvent at an elevated temperature, thereby producing a melt containing quaternary bases, treating said melt with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate at a temperature of substantially 100 C. for a relatively long period of time in order to convert said quaternary bases into the desired product, extracting the resultant mixture while still warm with benzene, and then removing the benzene to isolate the desired product.

12. A process for producing-l phenyl-2,3-dimethyl-S-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with dimethyl sulphate in the absence of a solvent at an elevated temperature, thereby producing a melt, dissolving said melt, adding thereto a solution of a caustic alkali, extracting the resultant mixture with benzene, separating out the quaternary bases formed as a result of the reaction, treating said quaternary bases with an excess amount of a compound of the group consisting of an alkali-metal hydroxide and an alkali-metal carbonate for a relatively long period of time at.

substantially 100 C. in order to convert said bases into the desired product, extracting the resultant mixture while it is still warm with benzene, and then removing the benzene to isolate the product.

13. A process for producing1-phenyl-2,3-\di methyl-5-pyrazolone which comprises the steps of reacting 1-phenyl-3-methyl-5-pyrazolone with p-toluene-sulphonic-acid-methyl-ester in the absence of a solvent at an elevated temperature thereby producing a melt, dissolving said melt in hflt wflilel, acidulating the resulting solution, cooling said mixture in order to crystallize the first recovered portion of the p-toluene-sulphonate of the 1-phenyla2,3edimethyl-5-pyrazolone base, fil-,

tering oil the said crystallized sulphonate, con-,

centrating the filtrate obtained, heating said fil trate for a relatively long period of time at substantially 100 C. withan excess amountv of a compound of the group consisting of an alkaliv warm with benzene, and then removing the ben-,- 20

zene to recover the desired product.

BAPTIST REUTER. 

